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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Here, we characterized the role of cyclic diguanylate (c-di-GMP) and EPS (PEL) overproduction in the wspF mutant phenotypes of P. aeruginosa PA14 (wrinkly appearance, hyperadherence, impaired motilities, and reduced virulence in acute infections).

We confirmed that the elevated c-di-GMP level plays a key role in all the wspF mutant phenotypes listed above, as assessed by ectopic expression of a c-di-GMP-degrading phophodiesterase (PvrR) in the wspF mutant.

In contrast, PEL EPS, which is overproduced in the wspF mutant, was necessary for wrinkly appearance and hyperadherence, but not for the impaired flagellar motilities and the attenuated virulence of the wspF mutant.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation.

We have recently identified the glycoprotein M6a as a stress-responsive gene in the hippocampal formation.

This gene is down-regulated in the hippocampus of both socially and physically stressed animals, and this effect can be reversed by antidepressant treatment.

In the present work, we analyzed the biological function of the M6a protein.

Immunohistochemistry showed that the M6a protein is abundant in all hippocampal subregions, and subcellular analysis in primary hippocampal neurons revealed its presence in membrane protrusions (filopodia/spines).

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The case of a 12 yr old female with bcr-abl positive chronic myeloid leukemia who subsequently developed a fatal AML-M6b (pure erythroleukemia) blast crisis is presented.

The case is unique for its rarity of occurrence and for the striking resemblance that the circulating proerythroblasts showed to the giant cells characteristically seen in Parvovirus B19-induced acutepure red cell aplasia.

This is, to the best of our knowledge, the first description of such cells in a blast crisis of chronic myeloid leukemia.

Enhanced M6a-Ib expression in the medial prefrontal cortex (in areas prelimbic and infralimbic cortex) might be interpreted as a compensatory mechanism in response to changes in axonal projections from the hippocampus.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The interaction of mu-opioid receptor (MOPr) with the neuronal membrane glycoprotein M6a is known to facilitate MOPr endocytosis in human embryonic kidney 293 (HEK293) cells.

To further study the role of M6a in the post-endocytotic sorting of MOPr, we investigated the agonist-induced co-internalization of MOPr and M6a and protein targeting after internalization in HEK293 cells that co-expressed HA-tagged MOPr and Myc-tagged M6a.

We found that M6a, MOPr, and Rab 11, a marker for recycling endosomes, co-localized in endocytotic vesicles, indicating that MOPr and M6a are primarily targeted to recycling endosomes after endocytosis.

Furthermore, co-expression of M6a augmented the post-endocytotic sorting of delta-opioid receptors into the recycling pathway, indicating that M6a might have a more general role in opioid receptor post-endocytotic sorting.

The enhanced post-endocytotic sorting of MOPr into the recycling pathway was accompanied by a decrease in agonist-induced receptor down-regulation of M6a in co-expressing cells.

We tested the physiological relevance of these findings in primary cultures of cortical neurons and found that co-expression of M6a markedly increased the translocation of MOPrs from the plasma membrane to intracellular vesicles at steady state and significantly enhanced both constitutive and agonist-induced receptor endocytosis.

In conclusion, our results strongly indicate that M6a modulates MOPr endocytosis and post-endocytotic sorting and has an important role in receptor regulation.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

M6a overexpression in rat primary hippocampal neurons induces the formation of filopodial protrusions that could be spine precursors.

As the filopodium and spine motility has been associated with synaptogenesis, we analysed the motility of M6a-induced protrusions by time-lapse imaging.

Our data demonstrate that the motile protrusions formed by the neurons overexpressing M6a were more abundant and moved faster than those formed in control cells.

When different putative M6a phosphorylation sites were mutated, the neurons transfected with a mutant lacking intracellular phosphorylation sites bore filopodia, but these protrusions did not move as fast as those formed by cells overexpressing wild-type M6a.

This suggests a role for M6a phosphorylation state in filopodium motility.

Furthermore, we show that M6a-induced protrusions could be stabilized upon contact with presynaptic region.

The behavior of filopodia from M6a-overexpressing cells and control cells was alike.

Thus, M6a-induced protrusions may be spine precursors that move to reach presynaptic membrane.

We suggest that M6a is a key molecule for spine formation during development.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Glycoprotein M6a is a neuronally expressed member of the proteolipid protein (PLP) family of tetraspans.

In vitro studies suggested a potential role in neurite outgrowth and spine formation and previous investigations have identified M6a as a stress-regulated gene.

To investigate whether the distribution of M6a correlates with neuronal structures susceptible to alterations in response to stress, we localized M6a expression in neurons of hippocampal formation, prefrontal cortex and cerebellum using in situ hybridization and confocal immunofluorescence microscopy.

In situ hybridization confirmed that M6a is expressed in dentate gyrus and cerebellar granule neurons and in hippocampal and cortical pyramidal neurons.

Confocal microscopy localized M6a immunoreactivity to distinct sites within axonal membranes, but not in dendrites or neuronal somata.

Moreover, M6a colocalized with synaptic markers of glutamatergic, but not GABAergic nerve terminals.

The present neuroanatomical data demonstrate that M6a is an axonal component of glutamatergic neurons and that it is localized to distinct sites of the axonal plasma membrane of pyramidal and granule cells.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The distinction between RAEB, RAEB-T and AML M6a is difficult when erythroblasts in the bone marrow (BM) exceed 50%.

We analyzed 19 children (2 RAEB, 13 RAEB-T and 4 AML M6a) enrolled in a prospective pathological central review in Japan and divided them into two groups according to the myeloblasts percentage among non-erythroid cells in BM: group A (n = 8), 5-19% myeloblasts; group B (n = 11), 20% or more myeloblasts.

Six with group A and seven with group B treated with AML type chemotherapy achieved complete remission.

Five with group A and seven with group B undergoing SCT are alive at a median of 3 years after diagnosis.

Erythroblast-rich RAEB and AML M6a in children have similar characteristics and may belong to a single disease entity.

Southern blot analyses revealed that homologues to these pectate lyase genes were broadly distributed in Meloidogyne species, and present as members of a small multigene family.

Mi-pel-1 and Mi-pel-2 encoded, respectively, predicted proteins of 271 and 280 amino acids, each of which was preceded by a signal peptide for secretion.

Interestingly, these pectate lyases showed diversity at the amino acid level, with only 31% identity and 49% similarity.

These pectate lyases were classified into the same family of pectate lyases with those of other phytoparasitic nematodes that contain four conserved regions characteristic of the class III pectate lyases of microbes.

In situ mRNA hybridisation analyses showed the transcripts of Mi-pel-1 and Mi-pel-2 accumulated exclusively within the subventral oesophageal gland cells of M. incognita.

These results indicated that these pectate lyases, like cellulases, could be secreted into plant tissues to facilitate the penetration and intercellular migration of M. incognita during the early stages of plant parasitism.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: e14592 Background: During the process of malignant transformation, the tumor cell adopts a new form of metabolism, characterized by aerobic glycolysis and altered TCA cycle flux, that enable it to meet the energetic and biosynthetic demands of proliferation.

METHODS: We have characterized the proliferative and metabolic effects of phenformin, a member of the biguanide family of compounds used in the treatment of diabetes, on the bcr-abl expressing K562 erythroleukemia cell line, and compared the resulting phenotype to those of imatinib and rapamycin, two targeted agents used in the treatment of malignant disease.

Phenformin treatment eliminated the mitochondrial contribution to anabolic metabolism, through inhibition of Complex I of the Electron Transport Chain, as demonstrated by reduced oxygen consumption and intracellular ATP levels.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Several groups have now shown that lentiviral (LV) vectors stably transmit the hβ/hγ-globin genes and large elements of the locus control region, resulting in correction of the murine thalassemia intermedia (TI) phenotype and survival of mice with the TM phenotype.

We observed a consistent twofold-higher hβ expression from insulated vectors in single-copy mouse erythroleukemia cell clones, an increase that resulted from reduced position effect variegation (PEV) and increased probability of expression from individual integrants.

These studies have important implications for vector design for clinical trials for gene therapy for hemoglobinopathies.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Although QS regulation of swarming and DNA release has been shown to play important roles in biofilm development, regulation of genes directly involved in biosynthesis of biofilm matrix has not been described.

Here, transcription of the pel operon, essential for the production of a glucose-rich matrix exopolysaccharide, is shown to be greatly reduced in lasI and rhlI mutants.

Co-expression of MOPr with M6a, but not with M6b or DM20, exists in many brain regions, further supporting a specific interaction between MOPr and M6a.

After opioid treatment M6a co-internalizes and then co-recycles with MOPr to cell surface in transfected human embryonic kidney 293 cells.

Moreover, the interaction of M6a and MOPr augments constitutive and agonist-dependent internalization as well as the recycling rate of mu-opioid receptors.

On the other hand, overexpression of a M6a-negative mutant prevents mu-opioid receptor endocytosis, demonstrating an essential role of M6a in receptor internalization.

In addition, we demonstrated the interaction of M6a with a number of other G protein-coupled receptors (GPCRs) such as the delta-opioid receptor, cannabinoid receptor CB1, and somatostatin receptor sst2A, suggesting that M6a might play a general role in the regulation of certain GPCRs.

Taken together, these data provide evidence that M6a may act as a scaffolding molecule in the regulation of GPCR endocytosis and intracellular trafficking.

[Title] The pel genes of the Pseudomonas aeruginosa PAK strain are involved at early and late stages of biofilm formation.

The pel genes encode proteins with similarity to components involved in polysaccharide biogenesis, of which PelF is a putative glycosyltransferase.

The pel genes were previously identified in the P. aeruginosa PA14 strain as required for the production of a glucose-rich matrix material involved in the formation of a thick pellicle and resistant biofilm.

However, in PA14, the pel mutants have no clear phenotype in the initiation phase of attachment.

It was shown that pel mutations in the PAK strain had little influence on biofilm initiation but, as in PA14, appeared to generate the least robust and mature biofilms.

Strikingly, by constructing pel mutants in a non-piliated P. aeruginosa PAK strain, an unexpected effect of the pel mutation in the early phase of biofilm formation was discovered, since it was observed that these mutants were severely defective in the attachment process on solid surfaces.

The pel gene cluster is conserved in other Gram-negative bacteria, and mutation in a Ralstonia solanacearum pelG homologue, ragG, led to an adherence defect.

And we found that these cell lines showed respective typical gene expression profiles and classified into clear four groups, PEL, TCL, BL, and normal PBMCs.

Even though there was only one line that was co-infected with both Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), KSHV seemed to govern the gene expression profile of the co-infected line.

These data suggested not only that established typical tumor cell lines show a distinct gene expression profile but also that this profile may be governed by certain viruses.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

A recent study revealed a subfamily of N6-adenine (m6A) methyltransferases that comprises a few functionally studied eukaryotic members acting on mRNA and prokaryotic members acting on DNA as well as numerous uncharacterized open reading frames.

Here, we report cloning and functional characterization of a prokaryotic member of this family encoded by transposon Tn1549 from Enterococcus spp.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title]PEL: an unbiased method for estimating age-dependent genetic disease risk from pedigree data unselected for family history.

Providing valid risk estimates of a genetic disease with variable age of onset is a major challenge for prevention strategies.

This article focuses on ascertainment through at least one affected and presents an estimation method based on maximum likelihood, called the Proband's phenotype exclusion likelihood or PEL for estimating age-dependent penetrance using disease status and genotypic information of family members in pedigrees unselected for family history.

We studied the properties of the PEL and compared with another method, the prospective likelihood, in terms of bias and efficiency in risk estimate.

For that purpose, family samples were simulated under various disease risk models and under various ascertainment patterns.

We showed that, whatever the genetic model and the ascertainment scheme, the PEL provided unbiased estimates, whereas the prospective likelihood exhibited some bias in a number of situations.

As an illustration, we estimated the disease risk for transthyretin amyloid neuropathy from a French sample and a Portuguese sample and for BRCA1/2 associated breast cancer from a sample ascertained on early-onset breast cancer cases.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

This screen identified the PA3885 mutant, which had 147-fold more biofilm than the wild-type strain.

Whole transcriptome analysis showed that loss of PA3885 activated expression of the pel locus, an operon that encodes for the synthesis of extracellular matrix polysaccharide.

Genetic screening identified that loss of PelABDEG and the PA1120 protein (which contains a GGDEF-motif) suppressed the phenotypes of the PA3885 mutant, suggesting that the function of the PA3885 protein is to regulate 3,5-cyclic diguanylic acid (c-di-GMP) concentrations as a phosphatase since c-di-GMP enhances biofilm formation by activating PelD, and c-di-GMP inhibits swarming.

These results show that the PA3885 protein responds to AHL signals and likely dephosphorylates PA1120, which leads to reduced c-di-GMP production.

This inhibits matrix exopolysaccharide formation, which leads to reduced biofilm formation; hence, we provide a mechanism for quorum sensing control of biofilm formation through the pel locus and suggest PA3885 should be named TpbA for tyrosine phosphatase related to biofilm formation and PA1120 should be TpbB.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Subtype C1 persistent infection of HHV-8 in a PEL patient.

PEL, a rare type of lymphoma constituting less than 5% of NHLs, has been recently identified as a distinct clinical and pathological entity among the B-cell lymphomas, with characteristic morphologic, immunophenotypic, molecular and viral features.

Using a combination of clinical, morphological, immunohistochemical features and molecular biology techniques in this study we document a PEL case with persistent HHV-8 of genotype C1 infection.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Pectate lyase (PL) is a potent cell wall-degrading enzyme known to play a role in the microbial infection of plants.

However, the PL gene (pel) was detected by Southern hybridization in four out of four P. syringae pv. glycinea strains examined.

A P. syringae pv. glycinea pel gene was cloned, sequenced, and predicted to encode a protein sharing 70%-90% identity in amino acid sequence with PLs produced by pectolytic pseudomonads and xanthomonads.

A series of amino acid and nucleotide sequence analyses reveal that (i) the predicted P. syringae pv. glycinea PL contains two regions in the amino acid sequence that may affect the formation of a beta-helix structure important for the enzyme activity, and (ii) the P. syringae pv. glycinea pel gene contains a single-base insertion, a double-base insertion, and an 18-bp deletion, which can lead to the synthesis of an inactive PL protein.

The altered pel sequence was also detected by polymerase chain reaction and nucleotide sequencing in the genomes of other pathovars of P. syringae, including phaseolicola and tagetis.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Integration of two essential virulence modulating signals at the Erwinia chrysanthemi pel gene promoters: a role for Fis in the growth-phase regulation.

Production of the essential virulence factors, called pectate lyases (Pels), in the phytopathogenic bacterium Erwinia chrysanthemi is controlled by a complex regulation system and responds to various stimuli, such as the presence of pectin or plant extracts, growth phase, temperature and iron concentration.

Eight regulators modulating the expression of the pel genes (encoding Pels) have been characterized.

Although many studies have been carried out, the mechanisms of control of Pel production by growth phase have not yet been elucidated.

Here we report that a fis mutant of E. chrysanthemi showed a strong increase in transcription of the pel genes during exponential growth whereas induction of expression in the parental strain occurred at the end of exponential growth.

This reveals that Fis acts to prevent an efficient transcription of pel genes at the beginning of exponential growth and also provides evidence of the involvement of Fis in the growth-phase regulation of the pel genes.

By using in vitro DNA-protein interactions and transcription experiments, we find that Fis directly represses the pel gene expression at the transcription initiation step.

In addition, we show that Fis acts in concert with KdgR, the main repressor responding to the presence of pectin compounds, to shut down the pel gene transcription.

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Moreover, terminal bronchiolar Clara injury, as evidenced by apical membrane blebs, was observed at relatively low concentrations, suggesting if this synthetic jet fuel is utilized, the current permissible exposure limit of 350 mg/m(3) for hydrocarbon fuels should cautiously be applied.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Antisense inhibition of a pectate lyase gene supports a role for pectin depolymerization in strawberry fruit softening.

It has been reported previously that inhibiting the expression of pectate lyase genes by antisense technology in strawberry (Fragaria x ananassa Duch.) fruit resulted in prolonged fruit firmness.

In this present study, three independent transgenic lines were identified exhibiting a greater than 90% reduction in pectate lyase transcript abundance.

These results indicate that pectate lyase plays an important degradative role in the primary wall and middle lamella in ripening strawberry fruit, and should be included in synergistic models of cell wall disassembly.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Pectate lyases catalyse the eliminative cleavage of de-esterified homogalacturonan in pectin, a major component of the primary cell walls in higher plants.

In the completed genome of Arabidopsis, there are 26 genes (AtPLLs) that encode pectate lyase-like proteins.

Interestingly, all PLL genes are expressed in flowers.

Analysis of expression of all PLL genes in seedlings treated with hormones, abiotic stresses and elicitors of defense responses revealed significant changes in the expression of some PLLs without affecting the other PLLs.

The stability of transcripts of PLLs varied considerably among different genes.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

This study was designed to characterize and compare the pulmonary effects in distal lung from a low-level exposure to jet propellant-8 fuel (JP-8) and a new synthetic-8 fuel (S-8).

A pulmonary function test performed 24h after the final exposure indicated that there was a significant increase in expiratory lung resistance in the S-8 mice, whereas JP-8 mice had significant increases in both inspiratory and expiratory lung resistance compared to control values.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The topology of the potential energy landscape (PEL) underlying the dynamics of a two dimensional off-lattice model for a heteropolymer is analyzed for different sequences of amino-acids.

A statistical characterization of the metastable minima and first-order saddles of the PEL highlights structural differences in the landscape of good and bad folding sequences and provides insight on the chain dynamics during folding.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

However, if the main function of m5C and m4C in bacteria is protection against restriction enzymes, the roles of m6A are multiple and include, for example, the regulation of virulence and the control of many bacterial DNA functions such as the replication, repair, expression and transposition of DNA.

Interestingly, even if adenine methylation is usually considered a bacterial DNA feature, the presence of m6A has been found in protist and plant DNAs.

Furthermore, indirect evidence suggests the presence of m6A in mammal DNA, raising the possibility that this base has remained undetected due to the low sensitivity of the analytical methods used.

This highlights the importance of considering m6A as the sixth element of DNA.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

PEL is an aggressive proliferation of B cells with poor prognosis.

We evaluated both in vitro and in vivo the potential role of angiogenic factors secreted by PEL cells, that is, their interaction with endothelial cells and their implication in the invasive behavior of tumoral cells.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Primary effusion lymphoma (PEL) was initially designated as a body-cavity-based lymphoma and recognized as a distinct clinical entity without a contiguous tumor mass.

PEL was first reported in patients with acquired immunodeficiency syndrome (AIDS) and the distinctive feature of PEL originally reported as a B-cell neoplasm characterized by infection of the tumor cells by human herpes virus 8 (HHV-8).

However, there have recently been several reports of PEL in patients without human immunodeficiency virus (HIV) or HHV-8 infection.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Epstein Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are found together in approximately 80% of primary effusion lymphomas (PEL), but their contribution to these cancers is unclear.

We found that dominant-negative derivatives of EBNA1 inhibited EBV-positive PEL cells from forming colonies.

Those rare PEL cells that proliferated after expression of the dominant-negative derivatives usually expressed these derivatives at low or undetectable levels and continued to maintain their EBV genomes.

Those proliferating cells expressing higher levels of the derivatives expressed mutant derivatives that could not bind DNA.

These findings indicate that EBV is required to sustain proliferation, as measured by colony formation of dually infected PEL cells.

Surprisingly, they did inhibit the colony-forming ability of EBV-negative, KSHV-positive PEL cells.

These findings indicate that the site-specific DNA-binding activity of EBNA1 or its derivatives when expressed efficiently in EBV-negative, KSHV-positive PEL cells inhibits their colony formation possibly through their binding to the KSHV genome.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Pelargonidin (PEL), a common anthocyanidin with estrogenic activity, was tested in HL-60 cells for its genotoxicity and possible antigenotoxic effects against 4-nitroquinoline 1-oxide (NQO), a potent mutagen and carcinogen which induces oxidative stress.

To take into account potential interactions between phytochemicals within normal human nutrition, we evaluated a combination of PEL with the nonestrogenic phytochemical chlorogenic acid (CLA), one of the most abundant polyphenols in the human diet.

PEL (< or = 2 microM) and CLA (< or = 800 microM) were nongenotoxic in the micronucleus test.

We observed significant antigenotoxic effects against NQO with both compounds, but no additive interaction of PEL and CLA.

In conclusion, the phytoestrogen PEL revealed antioxidative and antigenotoxic properties in HL-60 cells, but no significant additive interaction with the abundant nutritional polyphenol CLA under the tested conditions.

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In spite of recent advances in the treatment of KS, PEL and MCD represent therapeutic challenges.

Recent advances in dissecting the pathogenesis of these diseases have indicated that the viral cytokine IL-6 and the cellular cytokines/growth factors IL-10, IL-6, stromal cell-derived factor 1, and vascular endothelial growth factor are important contributors to the growth, survival, and spread of PEL and MCD and are therefore potential targets for drug development.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The disruption of the ousA gene encoding the major osmoprotectant uptake system highly enhanced bacterial virulence on potato tubers.

In the absence of oxygen, pectate lyase (Pel) production was significantly higher in the tissue macerated with the ousA- strain than with the wild type.

In minimal medium, ousA disruption enhanced Pel production and pelE expression only under micro-aerobiosis conditions.

The effect on Pel was reversed by reintroduction of the ousA gene.

The osmoprotectectants glycine betaine, proline betaine, and pipecolic acid are known to be taken up via OusA and to have an inhibitory effect on Pel production.

However, their effects on Pel activity were not (glycine betaine) or only weakly (proline and pipecolic acid) affected by ousA disruption.

Furthermore, no correlation was observed between their effects on Pel activities and their osmoprotection efficacies.

The evidence indicates that ousA and osmoprotectant effects on Pel are not linked to osmoregulation and that complex regulations exist between Pel production, ousA, and osmoprotection via compounds liberated during the plant infection.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

We show that the absence of miRNAs likewise can be used to determine tumor origin (miR-155) and proliferation state because tumor suppressor miRNAs (miR-222/221, let-7 family) were significantly down-regulated in primary effusion lymphoma (PEL) and in Kaposi sarcoma (KS), an endothelial cell tumor.

PEL and KS are associated with KS-associated herpesvirus infection.

Because many tumor suppressor proteins are wild-type in KS and PEL, down-regulation of multiple tumor suppressor miRNAs provides a novel, alternative mechanism of transformation.

Azidothymidine (AZT, zidovudine) and interferon-alpha (IFN-alpha) induce apoptosis in HHV-8+/EBV- PEL cells in culture, by induction of a tumor necrosis factor-related apoptosis inducing ligand (TRAIL) mediated suicide program and has been proposed as a therapy for herpesvirus-associated lymphomas.

Daily injection of AZT and IFN-alpha significantly increased mean survival time (MST) of PEL/SCID mice suggesting that induction of apoptosis in PEL cells in vivo may be exploited as an effective relatively non-toxic therapy targeting HHV-8 infected PEL.

These data demonstrate that the PEL/SCID mouse is an important preclinical model to characterize efficacy and anti-tumor mechanisms of new therapeutic targets in vivo and will be useful in the design and testing of agents in viral lymphoproliferative diseases.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

To better understand the molecular mechanisms underlying the dendritic cell (DC) defects in cancer, we analyzed which signaling pathway is implicated in the abnormal monocyte differentiation into DC determined by the presence of Primary effusion lymphoma (PEL) released factors.

Our results indicate that the DC, obtained in this condition, together with phenotypic abnormalities and reduced allostimulatory function, showed hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) and p38 mitogen-activated protein kinase (MAPK) molecules, in comparison to the DC differentiated in the absence of PEL-released factors.

The inhibition of p38 MAPK but not of STAT3 phosphorylation, with specific inhibitors, was able to revert the effect of the PEL-released factors on the DC phenotype.

This study suggests that p38 MAPK signaling pathway is an important contributor to the abnormal differentiation of DC in PEL.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Kaposi sarcoma-associated herpesvirus is the causative agent of PEL.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a critical role in cell proliferation and survival, and this pathway is dysregulated in many different cancers, including PEL, which display activated PI3K, Akt, and mammalian target of rapamycin (mTOR) kinases.

We compared different compounds that inhibit the PI3K/Akt/mTOR pathway in PEL.

Although compounds that modulated activity of only a single pathway member inhibited PEL proliferation, the use of a novel compound, NVP-BEZ235, that dually inhibits both PI3K and mTOR kinases was significantly more efficacious in culture and in a PEL xenograft tumor model.

[Publication-type] Case Reports; Journal Article; Review

[Publication-country] Denmark

[Number-of-references] 31

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Building up from experimental knowledge of the regulatory network of the pel genes in the bacteria E. chrysanthemi, we propose for the first time a qualitative modeling of the infectious transition of this bacteria when it is hosted in a plant.

We show that this infectious transition can be understood as the excitable dynamics of a metabolico-genetic network.

The latent stage is characterized by a moderate but unequivocal expression of the virulence gene, waiting for a number of conditions which have to fulfill in order to trigger a fully developed infection.

In the virulent state the bacteria synthesize a massive production of virulence factors including pectate lyases (Pel) which favor the invasion of the host plant tissues.

Moreover it can be interpreted with respect to the relatively complex structure of the binding sites of pel.

From the biological point of view, our simulations validate the picture that the promoter of pel has evolved to form a security device preventing a hastened expression of these virulent genes.

This first modeling of the regulation of pel genes opens the way to new confrontations between theoretical ideas with experiments and possible strategies to fight the soft-rot disease of plants.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

In order to improve the thermostability of the Penicillium expansum Lipase (PEL), the lipase encoding genes was mutated by site-directed mutagenesis.

A recombinant vector pAO815-ep8-K55R which contain double mutant genes was constructed by overlap extension PCR using the cDNA of a random-mutant lipase ep8 (a single site mutant) as the template and two special primers were used to generate another mutation site K55R.

The recombinant vector was transformed into Pichia pastoris GS115 by electroporation and the recombinant mutant GS-pAO815-ep8- K55R can secret double-mutant lipase PEL-ep8-K55R-GS into the medium when it was induced by Methanol.

The yield of the double-mutant lipase is 508 u/mL, which is 81% that of the wild type lipase PEL-GS (627 u/mL) and 55% that of random-mutant PEL-ep8-GS (924 u/mL).

The specific activity of double-mutant lipase is 2309.1 u/mg, which is similar to random-mutant lipase PEL-ep8-GS and the wild type lipase PEL-GS.

The optimum temperature of the double-mutant lipase is same with the wild type lipase PEL-GS and random-mutant lipase PEL-ep8-GS.

While the Tm of the double-mutant lipase is 41.0 degrees C, 2.3 degrees C higher than the wild type lipase PEL-GS and 0.8% higher than the random-mutant lipase PEL-ep8-GS, indicating that the double-mutant lipase PEL-ep8-K55R-GS has higher thermostability.

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Two out of seven (29%) PEL cell lines harbored a mutant p53 allele (BCBL-1 and BCP-1) which led to doxorubicin resistance.

Supporting this finding, chemical inhibition of p53 signaling in PEL led to doxorubicin resistance, and chemical activation of p53 by the Hdm2 antagonist Nutlin-3 led to unimpaired induction of p53 target genes as well as growth inhibition and apoptosis.

We found that expression of major histocompatibility complex class I (MHC-I) surface molecules was significantly decreased in PEL cells when compared with HHV8 negative lymphomas, irrespective of EBV infection.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The role of p53 in primary effusion lymphoma (PEL) is complicated.

Despite this interaction, we had found that p53 was functional in PEL, i.e., able to induce apoptosis in response to DNA damage (C. E.

To further elucidate the relationship between LANA, p53, and hdm2, we purified LANA complexes from PEL by column chromatography.

The half-life of p53 was not extended, which is in contrast to the half-life of simian virus 40 T antigen-transformed cells. p53:p53, LANA:p53, and LANA:LANA complexes coexisted in PEL, and each protein was able to bind to its cognate DNA element.

These data suggest that under normal conditions, p53 is inactive in PEL, thus allowing for exponential growth, but that this inactivation is driven by the relative stoichiometries of LANA, hdm2, and p53.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

HHV-8-associated solid lymphomas which develop in extracavitary sites during the course of primary effusion lymphoma (PEL) could represent the relapse of original PEL tumors in different anatomical sites, or newly occurring distinct HHV-8-associated lymphomas, such as multicentric Castleman disease-related microlymphomas.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Diffuse large B-cell lymphoma initially manifested by massive ascites and a small gastric lesion, clinically mimicking primary effusion lymphoma (PEL) in the abdominal cavity: a case report and review of the literature on Japanese PEL patients].

The patient was treated with chemotherapy including rituximab (R-CHOP-ESHAP) and injection of methotrexate and dexamethasone into the medullary cavity as well as radiation to the whole brain, and achieved complete remission 4 months later.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Primary effusion lymphoma (PEL) is a fatal malignancy, which typically presents as a lymphomatous effusion that later disseminates.

Rapamycin (Rapa), which targets mTOR (mammalian target of Rapa), is currently evaluated as a treatment for PEL, but the recent development of PEL in Rapa-treated post-transplant recipients questions the drug's use in PEL.

Here, we used a murine model of PEL effusion that mimics the human disease to investigate the anti-PEL activity of Rapa.

[Publication-country] United States

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The Dot/Icm type IV translocated Ankyrin B (AnkB) effector of Legionella pneumophila is modified by the host prenylation machinery that anchors it into the outer leaflet of the Legionella-containing vacuole (LCV), which is essential for biological function of the effector in vitro and in vivo.

In silico analyses of four sequenced L. pneumophila genomes revealed the presence of eleven other genes that encode proteins with a C-terminal eukaryotic CaaX prenylation motif.

Of these eleven designated Prenylated effectors of Legionella (Pel), seven are also found in L. pneumophila AA100.

We show that six L. pneumophila AA100 Pel proteins exhibit distinct cellular localization when ectopically expressed in mammalian cells and this is dependent on action of the host prenylation machinery and the conserved cysteine residue of the CaaX motif.

Five of the Pel proteins are injected into human macrophages by the Dot/Icm type IV translocation system of L. pneumophila.

Taken together, the Pel proteins are novel Dot/Icm-translocated effectors of L. pneumophila that are post-translationally modified by the host prenylation machinery, which enables their anchoring into cellular membranes, and the prenylated effectors contribute to evasion of lysosomal fusion by the LCV.

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PF898 is a strain of Penicillium expansum optimized for the high level production of Penicillium expansum lipase (PEL).

This PEL is unique compared with other lipases in several aspects, For example, the PEL shows low sequence identities (<30%) to all other known lipases, and high percentage of hydrophobic residues in the N-terminal region.

The PEL was purified to homogeneity and shown to be 28 kDa by SDS-PAGE.

The crystals have tetragonal lattice and unit-cell parameters of a=b=88.09 A, c=126.54 A.

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The aim of the present study was to evaluate the immunologic and virological parameters, including HHV-8 viremia, of 5 HIV-infected patients with PEL whose disease was diagnosed and treated at our institute.

Elastin stains were performed using histochemical and immunohistochemical methods to demonstrate the peritoneal elastic lamina (PEL), and evaluated with regard to assessment of the subtype of implant.

The elastin stains demonstrated the PEL in most anatomical sites other than the omentum and the bladder and were considered helpful in 44/80 (55%) cases.

The staining was non-contributory in most of the remaining biopsies, because the PEL was not identified.

CONCLUSIONS: Demonstration of the PEL using elastin stains can be useful in the subclassification of implants associated with ovarian SBT and is of most value in confirming the superficial distribution of non-invasive lesions.

However, evaluation is limited by the absence of a defined elastic layer in a proportion of biopsy specimens, possibly reflecting their superficial location, as well as absence of a distinct PEL in sites such as the omentum.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Our objective was to evaluate a gel system that uses unconcentrated urine specimens for protein electrophoresis (PEL) and immunofixation electrophoresis (IFE) in patients with monoclonal gammopathies.

For the study, 222 urine specimens were analyzed by our current PEL method (Helena Laboratories, Beaumont, TX) and by a system that recommends use of unconcentrated urine (Sebia, Norcross, GA).

There was a 97% concordance for detection of PEL abnormalities.

Cases with insufficient urine volumes for concentration (PEL, 7; IFE, 20) were analyzed in the Sebia gel system, and in 11 cases (PEL, 2; IFE, 9) an M protein was identified.High-resolution gel electrophoresis of urine using the Sebia system offers similar performance for detection, characterization, and quantification of M proteins when compared with our current gel system.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

In the present paper, the properties of Go-like models are investigated in terms of the potential energy landscape (PEL).

The non-native attractions of the beta-barrel forming BLN model 46-mer are scaled with a parameter 0 < or = lambda < or = 1, to make a continuous tuning of the PEL from multi-funneled and energetically frustrated at lambda = 1 to a perfect funnel including only topological frustration at lambda = 0.

2006, 97, 050601), and extensive inherent structure (IS) analysis, clearly demonstrates the evolution of the topography of the PEL.

The alteration of the PEL also induces a dramatic change in the folding mechanism, from a second-order-like collapse transition into a cooperative, first-order-like folding transition, occurring through a transient, intermediate state ensemble characterized by partially structured IS.

The appearance of multiple van der Waals loops in the statistical temperature of the Go-like model is associated with the development of the intermediate states.

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Here, we show that LANA2, a viral protein that is absolutely required for the viability and proliferation of KSHV-infected primary effusion lymphoma (PEL) cells, increases the levels of SUMO2-ubiquitin-modified PML and induces the disruption of PODs by a proteasome-mediated mechanism.

In addition, we demonstrate that this disruption is largely dependent on both the integrity of a SUMO interaction motif in LANA2 and the lysine 160 from PML.

Moreover, silencing of LANA2 expression in PEL cells by RNA interference led to an increase in the PML levels.

Finally, we demonstrate that LANA2 relieves PML-mediated transcriptional repression of survivin, a protein that directly contributes to malignant progression of PEL.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: Seventeen measurements of capsule shape and 3 of primary epidermal laminae (PEL) morphology (spacing, orientation and curvature) were made on right and left front hooves from 27 Standardbred and 25 Thoroughbred horses, and tested for breed differences.

Three laminar variables (spacing, orientation and curvature) were measured on each hoof for samples of 25 PEL in 5 circumferential and 4 proximodistal locations.

Between breeds, PEL differed in orientation and spacing primarily at the medial quarters and heels, and in curvature at both quarters (P<0.05).

These results support the concept that remodelling of PEL is, at least in part, stimulated and directed by varying stress or strain levels in the laminar junction.

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All KSHV-positive solid lymphomas exhibited PEL-like cell morphology.

To investigate the relationship of these disorders to PEL and to other AIDS-associated diffuse large cell lymphomas, KSHV-positive solid lymphomas were tested for the expression of a set of genes that were previously shown by gene profiling analysis to define PEL tumor cells.

The results showed that expression of this set of genes in KSHV-positive lymphomas is similar to that of PEL but distinct from KSHV-negative AIDS-associated diffuse large cell lymphomas.

Because pathobiological features of KSHV-positive solid lymphomas closely mimic those of PEL, our results suggest that KSHV-positive solid lymphomas should be considered as a tissue-based variant of classical PEL, irrespective of HIV status.

Treatment of PEL cells with MG-132 results in downregulation of S-phase kinase protein 2 (SKP2) and accumulation of p27Kip1.

Furthermore, MG-132 treatment of PEL cells causes Bax conformational changes, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosole.

Such cytochrome c release results in sequential activation of caspases and apoptosis, while pretreatment of PEL cells with universal inhibitor of caspases, z-VAD-fmk prevents cell death induced by MG-132.

Altogether, these findings suggest that MG-132 is a potent inducer of apoptosis of PEL cells via downregulation of SKP2 leading to accumulation of p27Kip1, resulting in cell cycle arrest and apoptosis and strongly suggest that targeting the proteasomal pathway may provide a novel therapeutic approach for the treatment of PEL.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title]Acuteerythroleukemia: diagnosis and management.

Acuteerythroleukemia is a rare subtype of acutemyeloid leukemia that has undergone several changes in classification over the past 30 years.

There are two subtypes of acuteerythroleukemia: the more common erythroid/myeloid subtype, defined by the presence of increased erythroid cells and myeloid blasts; and the rarer, pure erythroid subtype, characterized by expansion of immature erythroid cells only.

The erythroid/myeloid subtype of acuteerythroleukemia is closely related to acutemyeloid leukemia with myelodysplasia-related changes, and is frequently characterized by morphological dysplasia and complex karyotype.

Pure erythroleukemia is a very uncommon subtype of leukemia associated with a very poor response and survival to current available therapeutic agents.

Treatment results for this disease are suboptimal and new drugs are needed.

This article summarizes current knowledge in the field of acuteerythroleukemia.

[Publication-type] Journal Article; Review

[Publication-country] England

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

We introduce the ideal Gaussian glass-forming system as a model to describe the thermodynamics and dynamics of supercooled liquids on a local scale in terms of the properties of the potential energy landscape (PEL).

In this way it becomes possible to identify a relevant PEL parameter determining the kinetic fragility.

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[Publication-country] United States

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

During the first decade after the discovery of primary effusion lymphoma (PEL), sporadic and serial reports suggested that Kaposi-sarcoma-associated-herpesvirus/human-herpesvirus-8 (KSHV/HHV-8)-associated lymphomas in their liquid and solid presentation are clinically distinct, representing part of the spectrum of PEL.

In HIV-seropositive patients with serous effusions, these solid lymphomas were reported before the development of an effusion lymphoma and following resolution of PEL.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Parkinson's disease (PD) is a neuropathological and debilitating disorder involving the degeneration of mesencephalic dopaminergic neurons.

Neuroprotective effect of pelargonidin (Pel) has already been reported, therefore, this study examined whether Pel administration would attenuate behavioural and structural abnormalities and markers of oxidative stress in an experimental model of PD in rat.

Furthermore, the increase of nitrite levels induced by 6-OHDA, indicate the nitric oxide formation and free radicals production and the decrease of antioxidant defense enzyme superoxide dismutase (SOD) was non-significantly prevented by Pel (20mg/kg).

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The other region was coated with polyelectrolyte (PEL) to promote the adhesion of biomolecules including proteins and cells.

Resistance to the adsorption of proteins increased with the length of PEG and PLA chains because the longer PEG chain increased the PEG layer thickness and the longer PLA chain induced stronger interaction with the PEL surface.

The orthogonal functionality of prepared surfaces having PEL regions and background PEG-PLA regions resulted in rapid patterning of biomolecules.